{
  "abstract": "Distinct macrophage activation states play key roles in the formation and progression of heart allograft fibrosis. However, the exact molecular mechanisms that regulate the balance between inflammatory and pro-fibrotic macrophage responses during fibrosis remain poorly understood. Identifying and targeting the key molecule that regulates the differentiation of inflammatory and pro-fibrotic macrophages might be a pivotal strategy for mitigating fibrosis and prolonging allograft survival. Here, using single-cell sequencing analysis of human heart allografts fibrosis patient samples, we identified a population of macrophages that undergo epigenetic reprogramming through DNA methylation regulated by DNA methyltransferase DNMT1. DNMT1 small-molecule inhibitor 5-AzaC significantly attenuated graft fibrosis and prolonged allograft survival by inhibiting both inflammation and excessive tissue repair. Mechanistically, DNMT1-targeted macrophages suppress the DNA methylation level of the CpG island in the first intron of PTPRD, promoting PTPRD expression, which in turn inhibits the activity of STAT3 and STAT6 pathways, thereby suppressing the differentiation of inflammation and pro-fibrotic macrophages. Based on this, we developed a macrophage-targeted nanocarrier, MV/PEG-LPs, to load 5-AzaC, thereby enhancing its therapeutic precision for allograft fibrosis. Our results reveal a novel target, DNA methylation in macrophages, for the treatment of fibrosis-related diseases.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Organ Transplantation Clinical Medical Research Center of Hubei Province, Wuhan, China",
    "School of Pharmacy, Tongji Medical Colloge, Huazhong University of Science and Technology, Wuhan, China",
    "Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Naonao Yuan"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhibo Ma",
      "orcid": "0009-0006-0747-5916"
    },
    {
      "affs": [
        1
      ],
      "name": "Zihan Xue"
    },
    {
      "affs": [
        0
      ],
      "name": "Qingwen Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Xi Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Jing Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Yanping Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Shiqi Gu"
    },
    {
      "affs": [
        0
      ],
      "name": "Sichuan Yi"
    },
    {
      "affs": [
        1
      ],
      "name": "Yao Lu",
      "orcid": "0000-0003-1277-8816"
    },
    {
      "affs": [
        0
      ],
      "name": "Peixiang Lan",
      "orcid": "0009-0008-9481-0851"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/01ayvf3s4a9dv.bib",
  "cited_by": 0,
  "doi": "10.1038/s41420-026-03295-5",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737141/",
  "id": "01ayvf3s4a9dv",
  "issns": [
    "2058-7716"
  ],
  "landing_url": "https://doi.org/10.1038/s41420-026-03295-5",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2746|Transplantation: Methods and Outcomes"
    ]
  ],
  "openalex": "W7196988684",
  "pdf_url": null,
  "pmcid": "PMC13737141",
  "pmid": "42982818",
  "published": "2026-08-07",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/01ayvf3s4a9dv.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:25Z",
      "native_id": "PMC13737141",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41420-026-03295-5"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Transplantation: Methods and Outcomes",
      "subfield": "surgery"
    }
  ],
  "title": "DNMT1-targeted macrophages delivering drug-loaded nanoparticles attenuate heart allograft fibrosis via PTPRD-STAT3/6 axis",
  "title_text": "DNMT1-targeted macrophages delivering drug-loaded nanoparticles attenuate heart allograft fibrosis via PTPRD-STAT3/6 axis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:25Z",
  "url": "https://research.draconitic.com/paper/01ayvf3s4a9dv",
  "venue": "Cell Death Discovery",
  "versions": []
}